A focused update on emerging prognostic determinants in distal left main percutaneous coronary intervention

A distal location of the atherosclerotic plaque is one of the most powerful predictors of adverse events after left main angioplasty. However, bifurcations are not alike and may differ with regards to a number of variables, including the angle of the bifurcation, the presence of a ramus, the burden of downstream coronary artery disease, the involvement of stemming arteries and their mismatch. For these reasons, research is seeking to identify new specific predictors that are relevant to this patient population. Simple variables, including stenting strategy, SYNTAX (SYNergy between percutaneous coronary interventions with TAXus and cardiac surgery) score, angles and plaque distribution carry a prognostic value and may be useful to drive decisions in distal left main disease. We reviewed the evidences to date that specifically address the treatment of left main bifurcations, with emphasis on emerging prognostic determinants in this challenging scenario.     

L-citrulline Prevents Alveolar and Vascular Derangement in a Rat Model of Moderate Hyperoxia-induced Lung Injury

Background

Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.

Methods

Newborn rats were exposed to FiO₂?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.

Results

Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).

Conclusions

We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.     

Hypocomplementemic tubulointerstitial nephritis in IgG4-related disease

A novel lymphoproliferative disorder producing plasma cell expansion in the affected organ with fibrotic or sclerosing changes, known as 'IgG4-related disease', was defined in Japan by Umehara's group in 2010. We present the first case reported in Italy. In 2007, a 63-year-old man presented with epigastric pain and elevated serum lipase levels. Computed tomography of the abdomen revealed a Kuttner's tumor of the pancreas. The patient underwent a biliary-enteric anastomosis, and biopsy of the pancreas revealed massive infiltration of lymphocytes and plasma cells. The patient was diagnosed with chronic sclerosing pancreatitis. After one year, he began to show signs of sicca syndrome and at the same time developed progressive renal failure. Immunological tests revealed hypocomplementemia, and the renal biopsy specimen showed diffuse interstitial inflammation. The infiltrate was composed of lymphocytes, while infiltrating plasma cells showed immunoreactivity to IgG-4. Sialography using a radioisotope revealed severe involvement of the salivary glands, and Schirmer's test gave a positive result. This led us to diagnose hypocomplementemic tubulointerstitial nephritis in IgG4-related disease. Corticosteroid treatment resulted in rapid improvement including disappearance of the sicca syndrome and progressive amelioration of renal function. After six months, we discontinued steroid administration and started mycophenolate mofetil to maintain a low degree of immunosuppression. Follow-up after two years showed that this therapy continued to be quite effective in our patient.     

Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children,adolescents, and young adults with Charcot‐Marie‐Tooth disease

Long‐term studies of Charcot‐Marie‐Tooth (CMT) disease across the entire lifespan require stable endpoints that measure the same underlying construct (e.g., disability). The aim of this study was to assess the relationship between the CMT Pediatric Scale (CMTPedS) and the adult CMT Neuropathy Score (CMTNSv2) in 203 children, adolescents, and young adults with CMT. There was a moderate curvilinear correlation between the CMTPedS and the CMTNSv2 (Spearman's rho ρ = 0.716, p < 0.0001), although there appears to be a floor effect of the CMTNSv2 in patients with a milder CMT phenotype. Univariate analyses indicate that the relationship between the CMTPedS and CMTNSv2 scores improves with worsening disease severity and advancing age. Although one universal scale throughout life would be ideal, our data supports the transition from the CMTPedS in childhood to the CMTNSv2 in adulthood as a continuum of measuring lifelong disability in patients with CMT.     

Male–female differences in left-handedness in Sardinia,Italy

Males were consistently found to be more likely than females to report left-hand preference in single-hand tasks, but the literature reports negative results too. Using data from a large sample in Sardinia, we aimed at testing the links of left-handedness with sex, age, residence, and seasonality of birth. A total of 4239 participants (males = 1589; females = 2650) were recruited in public places such as high schools, university classes, or gyms in one of the major islands of Italy. Hand preference was established with the question: Which hand do you normally use to write legibly? The monthly distribution of births was studied with the Rayleigh test. In the sample, 270 female participants reported left-hand preference in writing (10.2%) versus 161 male participants (10.1%). Left-hand preference in writing was negatively related to age, with increasing left-hand preference in the younger generations. Left-hand preference in writing was not more common in urban than in suburban or rural settings. The month of birth was found to have a seasonal effect on the left-handed (p=.031) but not on the right-handed (p=.80) participants, and this seasonal effect was more evident in males (p=.04) than in females (p =.26). In our sample males were not more likely to report left-hand preference in writing than females. On the other hand, left-hand preference does vary by age and, in all likelihood, this is an effect of the reduced cultural pressure to write with the right hand in the younger generations.     

Common variable immunodeficiency: Crossroads between infections,inflammation and autoimmunity

Common variable immunodeficiency is a collection of diseases characterized by primary hypogammaglobulinemia. The causes of CVID are extremely heterogeneous and may affect virtually every pathway linked to B cell development and function. Clinical manifestations of CVID mainly include recurrent bacterial infections, but autoimmune, gastrointestinal, lymphoproliferative, granulomatous, and malignant disorders have also been frequently reported as associated conditions. We aimed to focus on the state of the art of the relationship between infections, inflammation and autoimmunity in CVID.